In recent years, the use of various herbs and/or herbal medical products for the prevention and treatment of diseases and alleviating the effects thereof have been gradually increasing in all societies. Throughout the human history, there have been and still are attempts for treating many diseases (diabetes, jaundice, dyspnea, etc.) by using some herbs. According to the records of the World Heath Organization (WHO), a large proportion of the world's population (70-80%) make use of herbs for therapeutic or prophylactic purposes. Additionally, around 25% of prescription drugs in developed countries are composed of plant-based active agents (vinblastine, reserpine, quinine, aspirin, etc.).
Particularly following the end of the 1990s, the discovery of new areas of use for medical and aromatic herbs and the increasing demand for natural products have increased the use potential thereof day by day.
Herbal medical products have long been in use for the treatment or prophylaxis of respiratory diseases. In the treatment or prophylaxis of these diseases which are typically caused by viruses, bacteria, and/or fungi, it is quite significant both to eradicate these harmful organisms and to boost the immune system of the affected individual. This is because the immune system is comprised of processes providing protection against diseases, as well as recognizing and eliminating the pathogenic and tumor cells in a living being. The system scans the organism against any kind of foreign substances, entering or contacting the former, from viruses to parasitic worms of a wide variety, and distinguishes them from the organism's own healthy cells and tissues. The immune system can even distinguish substances with very similar features from each other to such an extent that even proteins having a different amino acid can be distinguished from the equivalents thereof. The function of the immune system is primarily to prevent harmful foreign substances from entering the respective organism, or upon entry, to retain the substances at the place of entry, or to prevent or delay their spreading therein.
Hedera helix (English Ivy) is one of the plant species used in the production of herbal products for the treatment and prevention of diseases, and/or for the alleviation and/or elimination of the symptoms thereof. Hedera helix, comprising saponins, phenol, and alkaloids, is known to be used for the treatment of cough, parasites, skin diseases, bronchitis, and chronic respiratory tract diseases. Various studies have been performed to demonstrate the effect of Hedera helix on said diseases. For instance, Erik van Wyk and Michael Wink stated in “Medicinal Plants of the World” that the expectorant action of Hedera Helix works by stimulating the “nervus vagus” in the stomach, causing a cough response. A study by S. Fazio et al. published in the January 2009 issue of “Phytomedicine” tested a dried leaf extract on 9657 patients with acute and chronic bronchitis, including children. Accordingly, it was observed that following one week, cough and chest pain disappeared or improved in 95% of patients.
Pelargonium sidoides (African Geranium, Umckaloabo) is a plant species widely used in the treatment and prevention of, or in the alleviation and/or elimination of the symptoms of cold and respiratory tract disease (pharyngitis, sinusitis, acute bronchitis, tonsillitis). It was determined to be effective in increasing the generation of natural killer cells and tumor necrosis factor alpha, and to enhance the release of interferon beta. Pelargonium sidoides has antiviral properties strengthening the immune system. It further has both antibacterial effects and antioxidative properties against some bacteria. Apart from that, it was also reported to boost the immune system of the respective organism and to have expectorant action by increasing the ciliary beat frequency of respiratory epithelial cells. In a multicenter study conducted by the Pneumology Department of a German University Hospital (2000) on acute bronchitis patients, including adults, children, and infants, it was determined that an extract of the roots of Pelargonium sidoides reduced the severity of the symptoms after 7 days treatment from 6.3 to 0.9 according to the average bronchitis severity score. A study published in “Acta Paediatrica” in April 2010, showed that preparations extracted from herbal roots were much more effective in the treatment of acute bronchitis as compared to placebo. A study group of children aged 6 to 18 years, taking the herbal extracts experienced less coughing, sputum, and bed rest times versus placebo. By assessing the results of four placebo-controlled clinic trials, the researchers at the Medical Center, the University of Pittsburgh, concluded that a standardized extract of Pelargonium sidoides showed a much better performance in alleviating the bronchitis symptoms versus placebo in a 7-day treatment period.
In prior art, there are many formulations, which comprises herbal agents or combinations of herbal agents, are disclosed. For example, WO2009/011498 A1 discloses a composition for the treatment of infection in the form of a syrup comprising Pelargonium sidoides; EP1829548 A1 discloses a composition comprising an extract of Pelargonium sidoides; KEMMERICH BERND at al.: “Efficiency and tolerability of a fluid extract combination of thyme herb and ivy leaves and matched placebo in adults suffering from acute bronchitis with productive cough. A prospective, double-blind, placebo-controlled clinical trials” (ARZNEIMITTEL FORSCHUNG. DRUG RESEARCH, Acv EDITO CANTOR VERLAG, AULENDORF, DE, vol. 56, no. 9, 1 Jan. 2006, pages 652-660) discloses the use of the combination of extracts of thyme herb and ivy leaves for the treatment of acute bronchitis; FAZIO S et al.: “Tolerance, safety and efficacy of Hedera helix extract in inflammatory bronchial diseases under clinical practice conditions: A prospective, open, multicenter postmarketing study in 9657 patients”, (PHYTOMEDICINE, GUSTAV FISCHER VERLAG, STUTTGART, DE, vol. 16, no. 1, 2009, pages 17-24) discloses a composition in the form of a syrup comprising dried Hedera helix extract; HOFFMANN D et al.: “Efficacy of dry extract of ivy leaves in children with bronchial asthma—a review of randomized controlled trials”, (PHYTOMEDICINE, GUSTAV FISCHER VERLAG, STUTTGART, DE, vol. 10, no. 2-3, 2003, pages 213-220) discloses a composition comprising dried ivy leaves for the treatment of chronic airway obstruction in children suffering from bronchial asthma. Although that there are many formulations which comprise herbal agents or combinations of herbal agents, the effects of a formulation comprising Hedera helix extracts and Pelargonium sidoides extracts are not known yet.
Products to be used for medical purposes have to incorporate the elements of quality, efficiency, and reliability. A product can be a “medical” product only by having these elements. In order for a product prepared from a herbal source to be a medical product, it has to be prepared from an efficient and standardized extract, to have established pharmacological, clinical outcomes and toxicological data, and a determined stability. Therefore, it bears great significance to have a good stability for a product, produced from herbal sources, to be used in the treatment and prevention of diseases, or in the alleviation and/or elimination of the symptoms thereof.
Physical, chemical, and microbiological factors play role in the stability of medicaments or other products prepared for medical purposes. The stability issue is not dependent on a simple cause only, but emerges as a result of many factors. Factors such as the interaction of active agents contained in a product, the interaction of excipients among themselves or with active agents, pH, light, humidity, and temperature are among many elements which may influence the stability of such products.
Until recently, the researchers deemed considerable importance on the chemical stability of pharmaceutical products rather than the physical stability thereof and conducted many studies accordingly. In many instances, however, they could —show how important the changes in the physical structures of products are for the product quality, and for the durability of the technologic, microbiologic, and biopharmaceutical properties thereof. Accordingly, it was shown that primarily the physical stability of a product has to be maintained in order to sustain its quality and other features thereof, and therefore ensuring the physical stability during the development of pharmaceutical products is as important as, or sometimes more important than ensuring the chemical stability thereof.
Additionally, the physical properties taken into account in the evaluation of the physical stability of a product, particularly the taste, scent, color, clarity, uniformity, etc. of a product, also considerably influence the patient compliance. For this reason, when a novel formulation is developed, besides aiming a formulation of good physical stability, the physical properties of this formulation should be made ideal to provide high patient compliance.
Having said that, it is quite difficult to ensure the requirements mentioned above in the formulations comprising herbal agents. Due to some characteristic chemical, biological, and physical properties of herbal agents incorporated in a formulation, some difficulties are experienced in obtaining a formulation comprising such substances, and having both good physical stability and ideal features in terms of patient compliance.
The physical properties and the physical stability of a formulation are influenced directly from the characteristic properties of herbal agents contained therein. Some aspects of herbal agents contained in a formulation, such as having a bad taste, a bad scent, a bad color, and similar physical properties, becoming easily oxidized, and providing a suitable medium for the reproduction of microorganisms negatively influence the physical properties and physical stability of that formulation. Additionally, in case a formulation comprises a combination of herbal agents, a correct selection of the herbal agents bears great importance since more than one herbal agent present in the same formulation are capable to mutually affect their respective properties.
Under the light of the foregoing, it would be desirable to provide a formulation, as well as a process for the preparation of this formulation, comprising combinations of herbal agents, being capable to retain the physical stability for a long time, and having ideal physical properties in terms of patient compliance.
In detail, there is a need in the relevant art to a formulation comprising extracts of Hedera helix and Pelargonium sidoides and having ideal physical properties to ensure high patient compliance and good physical stability, as well as to a method for preparing this formulation, which is simple, cost-efficient and time-saving.